Marsman Rianne, Swinkels Sophie H N, Rosmalen Judith G M, Oldehinkel Albertine J, Ormel Johan, Buitelaar Jan K
Department of Psychiatry, Radboud University Nijmegen Medical Centre, P.O. Box 9101, 6500 HB Nijmegen, The Netherlands.
Psychoneuroendocrinology. 2008 Jul;33(6):789-98. doi: 10.1016/j.psyneuen.2008.03.005. Epub 2008 Apr 29.
Contradictory findings on the relationship between hypothalamus-pituitary-adrenal (HPA)-axis activity and externalizing behavior problems could be due to studies not accounting for issues of comorbidity and gender. In a population-based cohort of 1768 (10- to 12-year-old) early adolescents, we used a person-oriented approach and a variable-oriented approach to investigate whether comorbidity with internalizing behavior problems and gender moderate the relationship between HPA-axis activity (cortisol awakening response and evening cortisol levels) and externalizing behavior problems. We found that: (1) in early adolescents with pure externalizing behavior problems, there was a particularly strong effect of gender, in that girls showed significantly higher total cortisol levels after awakening (AUC(G) levels) and a significantly higher cortisol awakening response (AUC(I) levels) than boys. (2) Girls with pure externalizing behavior problems showed a significantly higher cortisol awakening response (AUC(I) levels) than girls without behavior problems or girls with comorbid internalizing behavior problems. This effect was absent in boys. (3) Externalizing behavior problems, in contrast to internalizing behavior problems, were associated with higher evening cortisol levels. This effect might, however, result from girls with externalizing behavior problems showing the highest evening cortisol levels. Overall, we were unable to find the expected relationships between comorbidity and HPA-axis activity, and found girls with pure externalizing behavior problems to form a distinct group with regard to their HPA-axis activity. There is need for prospective longitudinal studies of externalizing behavior problems in boys and girls in relation to their HPA-axis activity. It would be useful to consider how other risk factors such as life events and family and parenting factors as well as genetic risks affect the complex relationship between externalizing behavior problems and HPA-axis activity.
下丘脑-垂体-肾上腺（HPA）轴活动与外化行为问题之间关系的研究结果相互矛盾，这可能是由于研究未考虑共病和性别的问题。在一个基于人群的队列中，有1768名10至12岁的青少年，我们采用了以人为本的方法和以变量为导向的方法，来研究内化行为问题和性别的共病是否会调节HPA轴活动（皮质醇觉醒反应和夜间皮质醇水平）与外化行为问题之间的关系。我们发现：（1）在仅有外化行为问题的青少年中，性别影响尤为显著，即女孩觉醒后的总皮质醇水平（AUC(G)水平）显著高于男孩，皮质醇觉醒反应（AUC(I)水平）也显著高于男孩。（2）仅有外化行为问题的女孩的皮质醇觉醒反应（AUC(I)水平）显著高于没有行为问题或有共病内化行为问题的女孩。男孩则没有这种效应。（3）与内化行为问题不同，外化行为问题与夜间较高的皮质醇水平相关。然而，这种效应可能是由于有外化行为问题的女孩夜间皮质醇水平最高。总体而言，我们未能找到共病与HPA轴活动之间的预期关系，并且发现仅有外化行为问题的女孩在HPA轴活动方面形成了一个独特的群体。有必要对男孩和女孩的外化行为问题与HPA轴活动之间的关系进行前瞻性纵向研究。考虑其他风险因素，如生活事件、家庭和养育因素以及遗传风险如何影响外化行为问题与HPA轴活动之间的复杂关系，将是很有帮助的。
